Oxidation with RuO

Various substrates such as allyl alcohols, a,y3-unsaturated carbonyl compounds, and enol ethers undergo oxidative cleavage to afford the corresponding carbonyl compounds (Eqs. 3.35-3.37) [69-71], cis-Dihydroxylation occurs selectively, when the 

2-Dihaloalkenes are oxidized to a-diketones on a variety of norbomyl derivatives, which have been serving as highly potent and inextricable templates for strained polycyclic unnatural compounds (Eq. 3.40) [76]. 

Primary and secondary alcohols are oxidized to the corresponding carboxylic acids and ketones, respectively (Eqs. 3.41 and 3.42) [4c, 77]. Electrooxidation using a double mediatory system consisting of RUO4/RUO2 and C /Cr redox couples is also effective for oxidation of alcohols (Eq. 3.43) [77e]. 

Aromatic rings are smoothly converted to carboxylic acids (Eq. 3.44) [4c, 78]. An alkylphenyl group can be oxidized selectivity in the presence of an electron-deficient phenyl group such as a benzoyl group (Eq. 3.45) [78aj. 

Terminal alkynes undergo the similar oxidative cleavage to afford carboxylic acids (Eq. 3.46), vhile internal alkynes are converted to diketones (Eq. 3.47) [79]. 

---

For secondary alcohol groups in carbohydrates, although the use of Na(10 ) as co-oxidant with RuO or RuClj is cotmnon for generating RuO in these reactions, use of the sparingly soluble K(10 ) as co-oxidant is said to reduce over-oxidation [91, 171, 247, 280],... 

In 1953 Djerassi and Engle showed that stoich. RuOyCCy oxidised several sulfides to the corresponding sulfones [236]. Sulfilimines (R R S=NR ) were oxidised to sulfoximes R R S(=0)=NR by RuO /aq. Na(IO )/CH2Cl2 [432] oxidation of thianthrene-5-oxide with RuO /aq. Na(IO )/CCyO°C gave thianthrene-5,5-dioxide. Comparisons were made between the behaviour of RuO, CrO Cl and [MnO ] for these reactions, and 0-atom transfer with a possible intermediacy of [RuO ] was postulated [433]. Oxidations of RSPh to the sulfoxides and sulfones by stoich. RuOyaq. CH CN were studied a concerted mechanism may be involved for these and for similar oxidations by [RuO ] and [RuO ] " (Fig. 1.12) [434]. 

Although this method is quite old it has stood the test of time, and is the basis of many modem oxidations with RuO. Sharpless used it for oxidations of alcohols, ethers, aromatic rings and for aUcene cleavage, so clearly it has a high range of applicability. 

The reagent RuO /aq. Na(IO )/CCl oxidised a number of pyranoses and was the first catalytic Ru-based system for carbohydrates (Table 2.3) [2]. Although use of Na(10 ) as co-oxidant with RuO or RuClj is a common procedure for generating RuO in these reactions, it was noted that the use of the sparingly soluble K(IO ) in place of Na(10 ) as co-oxidant reduced over-oxidation [332] see also [330, 340, 341]. Conversion of pyranoses to lactones has been accomplished e.g. 2,4-di-O-benzyl-3-0-T)utyldiphenylsilyl-a,p-L-fucopyranose was oxidised by TPAP/NMO/ PMS/CHjCN to 2,4-di-0-benzyl-3-0- butyldiphenylsilyl-L-fuco-l,5-lactone (Fig. 2.17) [155]. 

Although Klaus discovered Ru in 1844 [1] it was not until 1860 that he isolated (and analysed) the volatile tetroxide, by passing Cl into a solution of Na iRuO ] [10]. It is usually prepared in situ from a convenient Ru compound such as the trichloride or dioxide with a suitable oxidant, a procedure used in all but the earliest organic oxidations using RuO. The pure compound was made by boiling aqueous RuClj with Na(Br03) and HCl and the vapour condensed in an ice-cooled container [204] from Ru(IV) or Ru(VI) species distilled with K3(S20g) [205] or from Cl with aqueous K2[RuO ] [203]. 

Owing to the very reactive nature of RuO relatively few solvents are suitable for its reactions. It is soluble in water to the extent of some 2% and is stable in such solutions, but reacts violently with diethyl ether, benzene and pyridine [236]. It has often been used catalytically in a biphasic system, with the co-oxidant in the aqueous layer. Under these circumstances the RuO formed from reduction of RuO by the substrate is re-oxidised at the organic - aqueous interface, so that oxidations with such systems can be much enhanced by stirring, shaking or sonication. In some cases (e.g. oxidation of aUcenes) it may be necessary to cool the reactants below room temperature, but in most cases ambient temperatures suffice, as indeed they do for the vast majority of organic oxidations catalysed by Ru complexes. 

The two-electron oxidation of primary alcohols RCH OH to aldehydes RCHO is rarer with RuO than is the four-electron process to RCOOH (2.1, 2.4.1.1 Table 2.1). Examples include the reagents RuCyaq. Na(Br03)/( Bu N)Br/CH2Cl2... 

The absence of any acyclic products from the reaction of cyclobutanol with RuO suggests that clean two-electron steps are involved [276]. Kinetic data for the oxidation of 2-propanol to acetone by RuOyaq. HCIO indicated that at moderate acidities the rate-determining step involves hydride abstraction, while at very high acid concentrations carbonium ions may be formed [277]. 

Early work with RuO -assisted oxidations was much concerned with alcohol functions in carbohydrates, and there are early but illuminating reviews on such reactions [60, 263]. 

Nakata showed that stoich. RuOyCCl oxidised steroidal diols to the corresponding ketones [237] electrogenerated RuO from RuO /aq. NaCl/Na(H3PO ) pH 4/ Pt electrodes converted diols to lactones and keto acids (Tables 2.1-2.4) [267] and RuCyaq. 10(0H)3/CC1 -CH3CN oxidised 3-(benzyloxy)-l,2-octanediol to the acid (Tables 3.4, 3.5) [107]. A diol was converted to a lactone by stoicheio-metric oxidation with RuOyCCl as part of the total synthesis of the quassinoid ( )-amarolide [82],... 

The first observation of the c/x-dihydroxylation reaction with RuO was made by Sharpless et al. in 1976, who noted that E and Z-cyclododecene were oxidised by stoich. RuO /EtOAc/-78 C to the threo and erythro diols [299]. Later RuCyaq. Na(IO )/EtOAc-CH3CN/0 C was used and reaction conditions optimised for many alkenes [300] a useful paper with good practical examples discusses the scope and limitations of the procedure (Table 3.2) [301]. Later oxidations were done with stoich. RuOyaq. acetone/-70 C [302] the same reagent converted A, and A steroids to cw-diols, ketones or acids [303], while RuO /aq. Na(10 )/acetone gave diones and acids [304]. 

A few other oxidations involve no C=C bond cleavage. Cti-9-octadecene gave 9.10-diketo-octadecane with RuO /aq. Na(C10)/( Bu N)Br/CHjCl2 [324], while cyclo-octene was oxidised by RnCyaq. Na(10 )/DCE to 8-oxo-octanal [325]. Oxidation of A -, and A - steroids using RuO /aq. Na(10 )/acetone gave cis-diols, diones and acids [303] while RuO /aq. Na(10 )/CHjCyCH3CN oxidised 2,3-dichlorodecene to decane-2,3-dione [326]. 

Optically active A-ethyl and A-benzylpiperidine gave the 2,6-diones with RuO / aq. Na(IO )/CCl (Table 5.1) [404,405]. Regiospecific oxidations of 2-substimted -... 

The oxidation is first order with respect to catalyst and alcohol, while the order with respect to NMO is fractional. A rate expression was derived and formation of a catalyst snbstrate complex proposed [500]. Oxidation of 2-propanol to acetone (and other secondary alcohols) by stoich. TPAP/CH Cl may be anto-catalytic the initial redaction product (RuO ) may form an adduct [Ru0. nRu02] with [RuO ]. The initially slow rate of oxidation by TRAP accelerated sharply as the concentration of product built up and then decreased near the end of the reaction because of the lower concentration of reactants, giving a bell-shaped curve typical of autocatalytic reactions [501]. 

Benzyl-alkyl, dialkyl, cyclic and acyclic ethers were converted to esters or lactones by RuO or [RuO ] (RuClj/aq. Na(C10) or Ca(C10)j/CH2Cl2). It was not stated whether RuO or [RuO ] was the effective oxidant, but oxidation of jb-methoxy-benzyhnethyl ether apparently involved a one-electron transfer process, which might be more likely to occur with [RuO ] [426],... 

Hydrated RuO is often used to generate RuO, [RuO ] or [RuO ] using cooxidants such as periodate or bromate. There are many examples in this and subsequent chapters of the use of RuOj.nH O as starting material with co-oxidants such as Na(IO ) for organic oxidations. Surprisingly, RuO was found to be inactive as an oxidation catalyst as RuOj.nHjO/NMO/acetone or DMF [647]. Oxidation of benzyl alcohol to benzaldehyde was effected with RuO or RuCljA Bu bOCl/aq. H O / CHjCy60°C [648]. 

In this short section brief experimental details are given for the in situ preparations of RuO, [RuO ] and [RuO ], the isolation of solid TPAP and of tra 5-Ru(0)3(bpy) 103(011)3 I.5H3O. There are also brief notes on specific oxidation procedures using these oxidants with which the author has had some experience. There are several good, practically explicit references in the literature to procedures with Ru oxidants, e.g. that by Haines [51, 202], Courtney [60] and by Lee and van der Engh [203],... 

Examples of such oxidations are listed in Table 2.3 with furanoses listed first in a roughly alphabetical arrangement mainly by substituent groups of products. Some large-scale oxidations (> 1 g) are listed in the first column. The effective oxidant in most cases is RuO, with a few by [RuO ] or [RuO ] . For oxidations by RuO the overall stoicheiometry of the reaction was shown [312] to be... 

Oxidation of 1,5-dienes to c -tetiahydrofurandiols was accomplished with RuO /aq. Na(10 )/acetone-EtOAc thus 2,5-dimethyl-1,5-hexadiene gave tetrahydrofurandiol, geranyl acetate yielded cw-tetrahydrofurandiol, and trans, tra 5-2,6-dimethyl-2,6-octadiene-l,8-diol diacetate (1) gave tetrahydrofuran ketol diacetate (2) (Fig. 3.12 cf. mech. Ch. 1) [174],... 

The isoprenoid polyenes famesyl acetate, geranyl acetate and squalene underwent oxidative poly cyclisation to bis-, tris- and penta-tetrahydrofurans with RuO /aq. Na(IO )/CH3CN-EtOAc [185]-[188]. This oxidative polycyclisation of squalene with RuO was shown to lead to the cis-threo-cis-threo-trans-threo-trans-threo-trans penta-tetrahydrofuranyl diol product, this configuration being determined by 2D-NMR (Fig. 3.14) [185]-[188] cf mech. Fig. 1.8 [185]. 

As with alkene cleavage the main reagent for alkyne oxidations is RuO. Oxidative cleavage of alkynes by a variety of reagents has been reviewed [4, 6, 12, 14, 15], The first oxidation of alkynes was noted by Pappo and Becker in 1956 they showed that l,2-fc/x(l-acetoxycyclohexyl)ethyne (2) (Fig. 1.5) gave the diketone. Minimal experimental details were given [195],... 

---